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5dwz

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Structural and functional characterization of PqsBC, a condensing enzyme in the biosynthesis of the Pseudomonas aeruginosa quinolone signal

Structural highlights

5dwz is a 8 chain structure with sequence from Pseudomonas aeruginosa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.04Å
Ligands:	, , , , , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PQSC_PSEAE Required for the biosynthesis of the quorum-sensing signaling molecules 2-heptyl-4(1H)-quinolone (HHQ) and 2-heptyl-3-hydroxy-4(1H)-quinolone (Pseudomonas quinolone signal or PQS), which are important for biofilm formation and virulence. The PqsC/PqsB complex catalyzes the condensation of 2-aminobenzoylacetate (2-ABA) and octanoyl-CoA to form HHQ. First, PqsC acquires an octanoyl group from octanoyl-CoA and forms an octanoyl-PqsC intermediate. Then, together with PqsB, it catalyzes the coupling of 2-ABA with the octanoate group, leading to decarboxylation and dehydration, and resulting in closure of the quinoline ring.^[1] ^[2]

Publication Abstract from PubMed

Pseudomonas aeruginosa produces a number of alkylquinolone-type secondary metabolites best known for their antimicrobial effects and involvement in cell-cell communication. In the alkylquinolone biosynthetic pathway, the beta-ketoacyl-(acyl carrier protein) synthase III (FabH) like enzyme PqsBC catalyzes the condensation of octanoyl-coenzyme A and 2-aminobenzoylacetate (2-ABA) to form the signal molecule 2-heptyl-4(1H)-quinolone. PqsBC, a potential drug target, is unique for its heterodimeric arrangement and an active site different from that of canonical FabH-like enzymes. Considering the sequence dissimilarity between the subunits, a key question was how the two subunits are organized with respect to the active site. In this study, the PqsBC structure was determined to 2A resolution, revealing that PqsB and PqsC have a pseudo 2-fold symmetry that unexpectedly mimics the FabH homodimer. PqsC has an active site comprised of Cys129 and His269, and the surrounding active site cleft is hydrophobic in character and approximately twice the volume of related FabH enzymes which may be a requirement to accommodate the aromatic substrate 2-ABA. From physiological and kinetic studies, we identified 2-aminoacetophenone as a pathway-inherent competitive inhibitor of PqsBC, whose fluorescence properties could be used for in vitro binding studies. In a time-resolved setup, we demonstrated that the catalytic histidine is not involved in acyl-enzyme formation, but contributes to an acylation-dependent increase in affinity for the second substrate 2-ABA. Introduction of Asn into the PqsC active site led to significant activity toward the desamino substrate analog benzoylacetate, suggesting that the substrate 2-ABA itself supplies the asparagine-equivalent amino function that assists in catalysis.

PqsBC, a condensing enzyme in the biosynthesis of the Pseudomonas aeruginosa quinolone signal: crystal structure, inhibition, and reaction mechanism.,Drees SL, Li C, Prasetya F, Saleem M, Dreveny I, Williams P, Hennecke U, Emsley J, Fetzner S J Biol Chem. 2016 Jan 25. pii: jbc.M115.708453. PMID:26811339^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Dulcey CE, Dekimpe V, Fauvelle DA, Milot S, Groleau MC, Doucet N, Rahme LG, Lepine F, Deziel E. The end of an old hypothesis: the pseudomonas signaling molecules 4-hydroxy-2-alkylquinolines derive from fatty acids, not 3-ketofatty acids. Chem Biol. 2013 Dec 19;20(12):1481-91. doi: 10.1016/j.chembiol.2013.09.021. Epub , 2013 Nov 14. PMID:24239007 doi:http://dx.doi.org/10.1016/j.chembiol.2013.09.021
↑ Drees SL, Li C, Prasetya F, Saleem M, Dreveny I, Williams P, Hennecke U, Emsley J, Fetzner S. PqsBC, a condensing enzyme in the biosynthesis of the Pseudomonas aeruginosa quinolone signal: crystal structure, inhibition, and reaction mechanism. J Biol Chem. 2016 Jan 25. pii: jbc.M115.708453. PMID:26811339 doi:http://dx.doi.org/10.1074/jbc.M115.708453
↑ Drees SL, Li C, Prasetya F, Saleem M, Dreveny I, Williams P, Hennecke U, Emsley J, Fetzner S. PqsBC, a condensing enzyme in the biosynthesis of the Pseudomonas aeruginosa quinolone signal: crystal structure, inhibition, and reaction mechanism. J Biol Chem. 2016 Jan 25. pii: jbc.M115.708453. PMID:26811339 doi:http://dx.doi.org/10.1074/jbc.M115.708453

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5dwz"

@@ Line 3: / Line 3: @@
 <StructureSection load='5dwz' size='340' side='right'caption='[[5dwz]], [[Resolution|resolution]] 2.04&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5dwz]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_aeruginosus"_(schroeter_1872)_trevisan_1885 "bacillus aeruginosus" (schroeter 1872) trevisan 1885]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DWZ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5DWZ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5dwz]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DWZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DWZ FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MPO:3[N-MORPHOLINO]PROPANE+SULFONIC+ACID'>MPO</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.04&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">pqsC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=287 "Bacillus aeruginosus" (Schroeter 1872) Trevisan 1885]), pqsB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=287 "Bacillus aeruginosus" (Schroeter 1872) Trevisan 1885])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MPO:3[N-MORPHOLINO]PROPANE+SULFONIC+ACID'>MPO</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-ketoacyl-[acyl-carrier-protein]_synthase_III Beta-ketoacyl-[acyl-carrier-protein] synthase III], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.180 2.3.1.180] </span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5dwz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dwz OCA], [https://pdbe.org/5dwz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dwz RCSB], [https://www.ebi.ac.uk/pdbsum/5dwz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dwz ProSAT]</span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5dwz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dwz OCA], [http://pdbe.org/5dwz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dwz RCSB], [http://www.ebi.ac.uk/pdbsum/5dwz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5dwz ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/PQSC_PSEAE PQSC_PSEAE] Required for the biosynthesis of the quorum-sensing signaling molecules 2-heptyl-4(1H)-quinolone (HHQ) and 2-heptyl-3-hydroxy-4(1H)-quinolone (Pseudomonas quinolone signal or PQS), which are important for biofilm formation and virulence. The PqsC/PqsB complex catalyzes the condensation of 2-aminobenzoylacetate (2-ABA) and octanoyl-CoA to form HHQ. First, PqsC acquires an octanoyl group from octanoyl-CoA and forms an octanoyl-PqsC intermediate. Then, together with PqsB, it catalyzes the coupling of 2-ABA with the octanoate group, leading to decarboxylation and dehydration, and resulting in closure of the quinoline ring.<ref>PMID:24239007</ref> <ref>PMID:26811339</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 26: / Line 27: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Drees, S L]]
+[[Category: Pseudomonas aeruginosa]]
-[[Category: Dreveny, I]]
+[[Category: Drees SL]]
-[[Category: Emsley, J]]
+[[Category: Dreveny I]]
-[[Category: Fetzner, S]]
+[[Category: Emsley J]]
-[[Category: Hennecke, U]]
+[[Category: Fetzner S]]
-[[Category: Li, C]]
+[[Category: Hennecke U]]
-[[Category: Prasetya, F]]
+[[Category: Li C]]
-[[Category: Saleem, M]]
+[[Category: Prasetya F]]
-[[Category: Williams, P]]
+[[Category: Saleem M]]
-[[Category: Pqsb]]
+[[Category: Williams P]]
-[[Category: Pqsc]]
-[[Category: Protein complex]]
-[[Category: Transferase]]

5dwz

From Proteopedia

Current revision

Structural and functional characterization of PqsBC, a condensing enzyme in the biosynthesis of the Pseudomonas aeruginosa quinolone signal

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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